Pancreatic Growth and Secretion. An Experimental Study on Growth Factors in Rat and Mouse

The pancreas is a central organ in the digestion of food as well as in glucose metabolism. Its two major functions are exocrine and endocrine secretion. These are meticulously regulated processes that depend on hormonal response to gastrointestinal contents and blood glucose levels through feedback mechanisms, but also to the status of pancreas in health and diseases. The present thesis aimed at further defining regulators of pancreatic growth, maintenance and secretion. A certain focus was set on the role of epidermal growth factor (EGF). The main regulator of pancreatic integrity and growth is cholecystokinin (CCK), which is regulated by a feedback mechanism involving pancreatic juice and bile. Inducing high plasma levels of CCK for 4 weeks, by a pancreatic-biliary diversion in rats, resulted in an increase in pancreatic weight and content of DNA, but not in an increased capacity to secrete amylase. The contents of amylase and lipase in the pancreas were decreased. Continuous infusion of EGF to mouse was found to increase pancreatic weight but not the contents of protein or amylase. A strong mitogenic stimulus on all cell types in the exocrine pancreas was found, along with increased mucosal thickness in the small intestine. No effect was seen in colon. Transforming growth factor alpha (TGF-α), which binds to the same receptor as EGF, induced hypertrophy in pancreas without affecting DNA synthesis. TGF-α gave a strong response in cell number when administrated to a human pancreatic cancer cell line, an effect blocked by an EGF receptor tyrosine kinase inhibitor, tyrphostin. EGF infused to rats was excreted in the bile and increased the joint biliary and pancreatic secretion rate in a dose dependent manner, an effect that was absent when bile was diverted. The EGF receptor has been demonstrated on the β-cells in rat. Injection of EGF decreased the blood insulin levels in rats. After glucose injection this effect was reversed. In summary, endogenous CCKemia stimulates pancreatic growth but decreases the content of pancraetic enzymes. Further, EGF probably, at least partly, exerts its effects on the pancreas and the proximal gastrointestinal tract in rats after excretion with bile. Bile and EGF seem to be important regulators of pancreatic growth and functions as well as the growth of the mucosa of the proximal gastrointestinal tract. EGF also affects blood insulin levels. EGF and TGF-α induce proliferation in a human pancreatic cell line, an effect inhibited by tyrphostins

Activated Protein C-Protein C Inhibitor Complex, Activation Peptide of Carboxypeptidase B and C-Reactive Protein as Predictors of Severe Acute Pancreatitis.

Introduction: The concentration of carboxypeptidase B activation peptide (CAPAP) is proposed to be a predictor of severe acute pancreatitis. The activated protein C (APC)-protein C inhibitor (PCI; APC-PCI) complex in plasma could be useful in detecting the hypercoagulative condition in severe acute pancreatitis. Method: In this prospective study, mild (n = 50) and severe (n = 9) cases of acute pancreatitis were compared with respect to levels of CAPAP and APC-PCI, and sorted in time intervals from onset of symptoms to sampling. The peak values of the C-reactive protein (CRP) within the 1st week were also compared. Results: CRP detected the severe cases with a sensitivity of 0.89 and a specificity of 0.74 (cut-off level 200 mg/l). In the interval 0-72 h, CAPAP could predict the severity of the disease in serum and urine (sensitivity 0.52/0.29, specificity 0.73/0.93, cut-off 2 nM/60 nM). The level of APC-PCI in plasma could predict the severe condition in the interval 0-24 h after the onset of symptoms (sensitivity 0.6, specificity 0.66, cut-off level 0.54 mug/l). Conclusion: Of the parameters explored, CRP is still the best biochemical marker to distinguish between severe and mild acute pancreatitis. CAPAP could be useful in combination with other tests, but the APC-PCI complex's diagnostic time interval is too short to be used in the clinical routine. and IAP

Epidermal growth factor induces cell proliferation in mouse pancreas and salivary glands

Epidermal growth factor (EGF) is a mitogenic stimulus in many tissues and occurs in large amounts in the pancreas and salivary glands. Whether EGF is mitogenic in the pancreas is controversial, and the EGF effect has not been studied in the salivary glands. Therefore, the aim of the present study was to investigate the possible effects on the pancreas and parotid and submandibular glands at different time intervals after exogenous EGF administration. Human recombinant EGF was infused subcutaneously by osmotic minipumps in three groups of mice (for 1, 3, and 7 days, respectively) at a dosage of 10 micrograms/kg/h (1.6 mumol/kg/h). Tritiated thymidine was infused intraperitoneally by osmotic minipumps for the same time periods, but only for the last 3 days in the 7-day group. After 1 day the pancreas increased in weight and the increase persisted throughout the study. No effect was seen on the parotid or submandibular gland wet weight. A slight transient increase in pancreas protein content was observed, whereas amylase content was unaffected. The labeling index of serous and ductal cells in the parotid gland increased from the third day. After 7 days, all cell types studied in the pancreas and parotid and submandibular glands were in a hyperproliferative state. The results show that EGF evoked a strong proliferative response on all cell types studied in the pancreas and parotid and submandibular glands

Prospective study of pain, quality of life and the economic impact of open inguinal hernia repair.

There are variations in quality of life (QoL) and reported risk of chronic pain after inguinal hernia repair. The aim of this study was to investigate the improvement in pain and QoL after open inguinal hernia repair, and the economic impact

Transforming growth factor alpha (TGF-alpha) increases cell number in a human pancreatic cancer cell line but not in normal mouse pancreas

BACKGROUND: The pancreas harbors growth factors such as the epidermal growth factor (EGF) family. The physiological and pathophysiological roles of growth factors in normal pancreas remain unsettled. Human pancreatic cancer overexpresses the EGF receptor, and the ligands EGF and transforming growth factor alpha (TGF-alpha). The aim of the present experiments was to study the effect of TGF-alpha in a pancreatic cancer cell line and in normal mouse pancreas. METHOD: The LN-36 cell line, established from a pancreatic duct cell adenocarcinoma, was incubated with TGF-alpha or EGF. The effect of an EGF receptor-specific, tyrosine kinase inhibitor (tyrphostin B56) with or without growth factors was also studied. The cell number was measured with the XTT-colorimetric method. TGF-alpha, the tyrphostins A25, B48, and B56, were in separate experiments infused during 1 wk to normal female mice by subcutaneous (sc) minipumps. RESULTS: The LN-36 cell line responded to TGF-alpha and EGF with increased cell number; +61% with 10(-10) M TGF-alpha and +34% with 10(-9) M EGF. Tyrphostin B56 at a concentration of 10(-5) M reduced the cell number by 76%, but when incubated together with growth factors the reduction was only 44% with TGF-alpha, and 39% with EGF. Infusion of TGF-alpha increased mouse pancreatic wet weight and protein content but was without effect on DNA synthesis, measured as incorporation of tritiated thymidine. Infusion of three different tyrphostins did not influence mice pancreas. CONCLUSION: The results support the role of TGF-alpha to maintain growth of pancreatic cancer cells by the EGF receptor. Infusion of TGF-alpha induced hypertrophy in normal mouse pancreas

Biliodigestive shunt evokes hyperCCKemia and trophic effects in the rat pancreas, but not in the liver or gastrointestinal tract

The influence of bile on the release of cholecystokinin (CCK) and, thereby, on the regulation of exocrine pancreatic function and growth is unsettled. The aim of this study was to elucidate the effect of long-term diversion of bile from the upper small intestine on CCK release and on the pancreas, liver, and gastrointestinal tract. A surgical biliodigestive shunt was performed in rats, diverting the bile flow directly to the middle of the small intestine. The animals were killed after 4 or 12 weeks. Plasma CCK and trophic effects on the pancreas, liver, and gastrointestinal tract were determined, as were the trypsin and chymotrypsin contents in the intestine. The CCK concentration in plasma increased 10-fold at both time points studied. The pancreas doubled its weight from 4 weeks onward. Also, pancreatic protein, DNA, and amylase contents were increased throughout the study. The liver and gastrointestinal tract were unaffected. Intraluminal bile plays a role in the feedback regulation of CCK release and is involved in this way in the control of pancreatic growth but has no similar effects on the liver or gastrointestinal tract

Laparoscopic versus open distal pancreatectomy (LAPOP): study protocol for a single center, nonblinded, randomized controlled trial

BackgroundEarlier nonrandomized studies have suggested that laparoscopic distal pancreatectomy (LDP) is advantageous compared with open distal pancreatectomy (ODP) regarding hospital stay, blood loss, and recovery. Only one randomized study has been conducted showing reduced time to functional recovery after LDP compared with ODP.MethodsLAPOP is a prospective randomized, nonblinded, parallel-group, single-center superiority trial. Sixty patients with lesions in the pancreatic body or tail that are found by a multidisciplinary tumor board to need surgical resection will be randomized to receive LDP or ODP. The primary outcome variable is postoperative hospital stay, and secondary outcomes include functional recovery (defined as no need for intravenous medications or fluids and as the ability of an ambulatory patient to perform activities of daily life), perioperative bleeding, complications, need for pain medication, and quality of life comparison.DiscussionThe LAPOP trial will test the hypothesis that LDP reduces postoperative hospital stay compared with ODP.Trial registrationISRCTN, 26912858. Registered on 28 September 2015.Funding Agencies|Medical Research Council of Southeast Sweden; County Council of Ostergotland (Region Ostergotland)</p

Compensation after umbilical hernia repair : prosthesis and non-prosthesis claims

Based on solid evidence, mesh prosthesis reinforcement has reduced the risk of recurrence after umbilical hernia repair1–4, but less is known about the risk of complications or chronic pain4,5. Patients’ claims after surgery may represent a surrogate for poor outcome6. This study examined mesh prosthesis-related complications leading to economic compensation after elective umbilical hernia repair. Before the present study, it was hypothesized that prosthesis-related complications and chronic pain after elective umbilical hernia repair were important claim reasons leading to economic compensation